Evolutionary cell biology: cell cycle control in archaea
I am interested in the evolution of the eukaryotic cell. While it is widely accepted that eukaryotes are a genomic merger of a putative archaeal host and a bacterial endosymbiont, the origins of the complex organization of the eukaryotic cell- with its nucleus, specialized organelles, diversified cytoskeleton and membrane trafficking systems- remains one of the biggest mysteries in cell biology.
The original archaeal host was probably a TACK archaeum- a group of archaeal species that carry homologs of many eukaryotic genes involved in the fundamental processes of translation, transcription, replication, ubiquitin signaling, cell cycle control and cytoskeletal function. The primary TACK model systems are Sulfolobus species, of particular interest for their phasic cell cycle reminiscent of eukaryotes and their use of the ESCRTIII complex to carry out cell division. Sulfolobus is a challenge to work with because of its small size (1 um) and extreme growth conditions (70C and a pH of 2.5). We are developing a new experimental platform to image Sulfolobus live using super-resolution techniques. Using this platform in conjunction with a rapidly growing genetic toolkit, we hope to gain insights into the regulation of the Sulfolobus cell cycle, and eventually an understanding of the evolutionary trajectory that led from the original archaeal cell cycle to the one regulating division in eukaryotes today.
Before my work here at UCL, I developed tools for quantitative cell biology: biosensors for translation control in human cells (Han et al. 2014), and novel statistical methods for RNAi screens in Drosophila (Dey et al. 2014, Gupta et al. 2014). During my PhD with Tobias Meyer at Stanford University, I developed a novel algorithm to extract functional modules in the human genome from patterns of shared evolutionary history, an extension of the technique termed phylogenetic profiling (Dey et al. 2015a, Dey et al. 2015b). I used this map to make functional predictions for uncharacterized human genes, a subset of which I verified experimentally in human cell lines. I developed a keen interest in understanding the evolution of signaling networks and the origins of cellular architecture, bringing me to the Baum lab in June 2015.